Abstract
Asymmetrically dividing stem cells inherit cellular components unequally to descending daughter cells. This creates two distinct cellular profiles originating from one mother cell. Among that, centrosomes are inherited according to their age in several types of stem cells. Centrosomes are the main microtubule organisation centres in the eukaryotic cytoplasm. Their two subunits duplicate once per cell cycle, which results in two differently aged centrosomes. However, it remains unknown how age can determine the fate of the organelle. Here, we studied asymmetries of spindle pole bodies (SPB), centrosome equivalents in budding yeast. To discriminate new and old SPB components, we used switchable fluorescent protein tags. By combining automated microscopy with unbiased high-content image analysis, we detected new asymmetry patterns of Nud1, the yeast homologue of the mammalian centrosome protein centriolin, and Spc97, a conserved adaptor protein for the microtubule receptor. Furthermore, our data shows a profound size asymmetry between the two cellular SPBs at early anaphase that is resolved by selective degradation of old components. Our findings support a dynamic and less conservative model of the SPB than previously thought with addition of new components to both SPBs and selective degradation of old subunits. For future studies, the developed methodology can be applied to high-throughput screenings for mutations that affect SPB inheritance patterns. This knowledge about SPB asymmetry formation might allow to find homologous regulators and mechanisms in mammalian cells and provide biological target sites for disease treatment.
Abstract
Stamceller som genomgår assymetrisk delning ärver olika mängd av vissa cellkomponenter. Detta leder till två distinkt olika celler som skiljer sig från varandra. Bland annat nedärvs centrosomer assymetriskt beroende av vilken ålder de har i flera olika typer av stamceller. Centrosomer är den huvudsakliga organisatören av cytoskelettet i den eukaryotiska cytoplasman. Centrosomernas två huvudkomponenter delar sig två gånger per cellcykel, vilket leder till två centrosomer av olika ålder. Det är dock ännu okänt hur åldern på centrosomerna kan bestämma dess öde. I denna studie har vi undersökt assymetrin hos jästcellens centromsomer.
